Our results suggest that 2'-fucosyllactose and 6'-sialyllactose reduce the symptoms of food allergy through induction of IL-10(+) T regulatory cells and indirect stabilization of mast cells. Thus, human milk oligosaccharides may have therapeutic potential in allergic disease.
Phenotypic differences in drug responses have been associated with known pharmacogenomic loci, but many remain to be characterized. Therefore, we developed next-generation sequencing (NGS) panels to enable broad and unbiased inspection of genes that are involved in pharmacokinetics (PKs) and pharmacodynamics (PDs). These panels feature repetitively optimized probes to capture up to 114 PK/PD-related genes with high coverage (99.6%) and accuracy (99.9%). Sequencing of a Korean cohort (n = 376) with the panels enabled profiling of actionable variants as well as rare variants of unknown functional consequences. Notably, variants that occurred at low frequency were enriched with likely protein-damaging variants and previously unreported variants. Furthermore, in vitro evaluation of four pharmacogenes, including cytochrome P450 2C19 (CYP2C19), confirmed that many of these rare variants have considerable functional impact. The present study suggests that targeted NGS panels are readily applicable platforms to facilitate comprehensive profiling of pharmacogenes, including common but also rare variants that warrant screening for personalized medicine.
The use of peptides as gatekeepers for payloads of mesoporous silica nanoparticles would allow triggering the release of guests by various biological stimuli. We investigated the effect of peptide conformation on their gatekeeping capability by employing two model peptides with a turn or a random structure. The conformation-dependent gatekeeping properties provided an opportunity to utilize the conformational conversion of peptides as a valuable motif for stimuli-responsive gatekeepers. Based on that investigation, we demonstrated that Fmoc-CGGC-SS-Si, which exhibited a zero-release property without any stimuli due to a turn-like conformation induced by the intramolecular disulfide bond, can be triggered to release guests by converting its conformation to a random structure, induced by reduction of the disulfide bond upon addition of glutathione. We further demonstrated that the conformational conversion of Fmoc-CGGC by Zn(II) ion can also be utilized as a triggering motif.
ABSTRACT--The dynamic response of sheet metals at high strain rate is investigated with a tensile split Hopkinson bar test using plate type specimens. The tension split Hopkinson bar inevitably causes some errors in the strain at grips with the plate type specimens, since the grip and specimens disturb the one-dimensional wave propagation in bars. To validate the experiment, the level of error induced from the grips is estimated by comparing the waves acquired from experiments with the Pochhammer-Chree solution. The optimum geometry of the specimen is determined to minimize the loading equilibrium error. High strain rate tensile tests are then performed with auto-body sheet metals in order to construct their appropriate constitutive models for use in crash-worthiness evaluation.
Influenza epidemics occur annually with variations in size and severity. Hospital-based Influenza Morbidity & Mortality was established to monitor influenza epidemics and their severity, which is composed of two surveillance systems: emergency room-based and inpatient-based surveillance. Regarding emergency room-based surveillance, influenza-like illness index (influenza-like illness cases per 1,000 emergency room-visiting subjects), number of laboratory-confirmed cases and the distribution of influenza types were estimated weekly. Inpatient-based surveillance included monitoring for hospitalization, complications, and mortality. The emergency room influenza-like illness index correlated well with the number of laboratory-confirmed influenza cases, and showed a bimodal peak at Week 4 (179.2/1,000 emergency room visits) and Weeks 13-14 (169.6/1,000 emergency room visits) of 2012. Influenza A was the predominant strain during the first epidemic peak, while influenza B was isolated exclusively during the second peak. In 2011-2012 season, the mean admission rate of emergency room-visiting patients with influenza-like illness was 16.3% without any increase over the epidemic period. Among the hospitalized patients with influenza, 33.6% (41 out of 122 patients) were accompanied by complications, and pneumonia (28.7%, 35 out of 122 patients) was the most common. Most fatal cases were caused by influenza A (96.2%) after the first epidemic peak. In conclusion, Hospital-based Influenza Morbidity & Mortality was effective for monitoring the trends in circulating influenza activity concurrently with its severity. In the 2011-2012 season, the influenza epidemic persisted for a ≥ 5-month period, with a bimodal peak of influenza A and B in sequence. Overall, influenza A was more severe than influenza B.
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